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Urticaria and angioedema are caused by immunoglobulin E- and non-immunoglobulin E-mediated release of histamine and other inflammatory mediators from mast cells and basophils. Diagnosis is made clinically, and anaphylaxis must be ruled out if urticaria or angioedema is present. A limited nonspecific laboratory workup should be considered unless elements of the history or physical examination suggest specific underlying conditions. The mainstay of treatment is avoidance of triggers when and if triggers are identified. The first-line pharmacotherapy is second-generation H1 antihistamines, which can be titrated to greater than standard doses., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Data on the course of urticaria in children exist, but there is a lack of sound data on patient management to ensure high-quality care., Methods: Retrospective secondary data analysis in the field of health care and epidemiology in children with urticaria based on routine data from a German health insurance company (DAK-Gesundheit). Data from insured persons under 18 years of age who were treated as outpatients or inpatients with a diagnosis of urticaria (according to ICD-10 classification) in 2010-2015 were included. The control group consisted of children without a corresponding diagnosis, in order to clarify health economic and care-related differences after adjusting for age and gender., Results: In 2015, 1904 (1.3%) of 151,248 insured minors had a diagnosis of urticaria. Of the children with urticaria, 70.9% visited at least one physician on an outpatient basis. Of these visits, 70.9% were made to a pediatrician, 52.5% to a general practitioner and 33.0% to a dermatologist; 11% were treated as inpatients. With a total of 151,248 insured persons, 1904 of whom were diagnosed with urticaria, 72.9% of children and adolescents with versus 28.9% without urticaria were treated topically or systemically in 2015, including 10.5% of children with urticaria vs. 2.6% without urticaria received topical therapy and 70.0% with urticaria received systemic therapy vs. 27.5% without urticaria with systemic therapy. The most commonly used oral medications for urticaria were cetirizine (44.2%), prednisolone (9.8%), and dimetindene (2.0%) . Topical methylprednisolone aceponate (49.8%) was prescribed most frequently. The therapy costs for systemic drugs was € 24.00 per patient, while topical drugs cost € 1.58 per patient., Conclusion: The lack of guidelines for the standardization of treatment in children still leads to ambiguities and different treatment concepts among the specialist groups, which must be eliminated in order to enable more efficient therapies. The treatment of chronic urticaria in children and adolescents is mainly carried out by pediatricians, general practitioners and dermatologists. Systemic and topical medications as well as inpatient services are the most important cost factors., (© 2024. The Author(s).)

The aim of this review is to present relevant trigger as well as augmentation factors that can induce or exacerbate urticaria on the basis of a current, PubMed-based literature search. In addition to a brief description of relevant influencing factors in acute and chronic inducible urticaria, the focus will be on chronic spontaneous urticaria. In particular, the aggravating role of medication, stress, food, psychological and metabolic comorbidities, infections and inflammation as well as hormonal processes will be discussed., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objective: Although acute urticaria (AU) and urticaria-like rash are commonly reported with COVID-19 infection, chronic spontaneous urticaria (CSU) triggered by COVID-19 is rare. The authors compared the features of COVID-19 infection-induced chronic CSU and AU to determine which patients' COVID-19 infection leads to CSU and possible indicators of chronicity., Methods: The authors retrieved the charts of patients diagnosed with AU or CSU following COVID-19 at the Urticaria Centers of Reference and Excellence and compared patients in terms of demographic characteristics, length of time between infection and onset of urticaria, duration of urticaria, COVID-19 disease severity, laboratory test results, vaccination, and treatment status., Results: A total of 92 patients were included in the study: 7 with CSU following COVID-19 and 85 with AU after COVID-19. The mean duration of urticaria for CSU and AU following COVID-19 was 13.0 ± 6.0 months and 7.1 ± 3.4 days, respectively. The average time between COVID-19 and the start of urticaria was longer in the CSU group (20.7 ± 3.9 days vs 4.5 ± 2.8 days, respectively; P = .000). No between-group differences were found for any other parameters., Conclusions: The onset of urticaria more than 2 weeks after COVID-19 infection may serve as an indicator for urticaria chronicity beyond 6 weeks and may help physicians predict the possible course of urticaria associated with COVID-19 infection. The relevance of basopenia and eosinopenia needs to be determined., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The phenotype of allergic diseases associated with Anisakis determines the pattern of cytokines related to antibody production. However, the role of serum IgA and the immunomodulatory mechanisms exerted by active infection of L3 or passive mucosal contact with A. simplex specific antigens has not been studied before. We measured serum cytokine by flow cytometry (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, IL-17A, TGF-β1) and antibody levels (IgE, IgG4, IgA) by ELISA against total and excretory-secretory (ES) antigens, Ani s 3,and the group of major allergens Ani s 1, Ani s 7, and Ani s 13 in sera from 10 patients with gastro-allergic anisakiasis (GAA), 11 Anisakis sensitization associated chronic urticaria (CU+) as well as 17 non-Anisakis-sensitized patients with chronic urticaria (CU-), compared with the urticaria control group (18 subjects). Specific IgE, IgG4 and IgA were high in the GAA, but IgA levels were significantly higher in the CU+ with respect the CONTROL group. We observed higher levels of the ratio IgA/IgG4 in CU+ than GAA group for Ani s 1, Ani s 7, Ani s 13 and ES. Furthermore, chronic urticaria (CU) patients showed significant lower levels of IL-10, IFN-γ and IL-17A than patients without CU. The anti-Ani s 13 IgA/IgG4 ratio correlated positively with pro-inflammatory cytokines and ratios (TNF-α, IL-17A, Th17/Th2, Type1/Type2 and TNF-α/IL-10) in CONTROL group. In general, Anti-Anisakis IgA/G4 ratio was high in CU patients. In conclusion, this study demonstrates the importance of serum IgA because it is associated with chronic urticaria independently of Anisakis sensitization., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Chronic spontaneous urticaria (CSU) is characterized by persistent or recurrent pruritic lesions that last more than 6 weeks. Patients with CSU may experience sleep disturbances, particularly due to itching. Biological rhythms (chronotypes) are categorized as morningness, intermediate, and eveningness types. This study evaluates the relationship between sleep quality, chronotype, and disease severity in CSU patients., Methods: The study included 53 CSU patients and 50 healthy controls. A sociodemographic data form was completed, and the disease severity was determined utilizing the Urticaria Activity Score over 7 days (UAS7). The Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), and Pittsburgh Sleep Quality Index (PSQI) scales as well as the Morningness-Eveningness Scale (MEQ) were applied to the participants., Results: The CSU group had a significantly higher body mass index (BMI) than that of the healthy control group. In terms of sleep and chronotype scales, compared to the control group, the CSU group had higher ISI scores as well as subscale scores on the PSQI subscales, with the exception of habitual sleep efficiency and total PSQI scores. There was no difference between MEQ scores. In the correlation analysis, the UAS7 and PSQI total scores were found to be correlated, whereas in the logistic regression analysis the estimated relative risk of BMI and PSQI total score for CSU was found to be 1.13 and 1.45, respectively., Conclusions: When dealing with CSU patients, it is necessary to conduct a sleep quality assessment as part of a holistic evaluation.

Background: Chronic inducible urticaria (CIndU) is a subtype of chronic urticaria (CU) which require specific physical or non-physical triggers to occur. They may be isolated or may coexist with chronic spontaneous urticaria (CSU). Despite their frequent appearance in dermatology clinics, there is scarce information on the distinguishing features among the most common subtypes of CIndU as well as isolated CIndU versus CSU plus CIndU., Objectives: To compare clinical and laboratory characteristics, and comorbid conditions among the most common CIndU types and isolated CIndU versus CSU plus CIndU., Methods: We retrospectively analysed CIndU patients and compared patients' demographic, clinical and laboratory characteristics across isolated CIndU, CSU plus CIndU, symptomatic dermographism (SD), cold urticaria (ColdU) and cholinergic urticaria (ChoU)., Results: A total of 423 patients (~70% isolated CIndU, ~30% CSU plus CIndU, ~5% mixed CIndU subtypes) were included in the study. The most frequent CIndU subtypes were SD (68.6%; 290/423), ColdU (11.4%; 48/423) and ChoU (10.9%; 46/423). Isolated CIndU patients were younger than CSU plus CIndU (33.74 ± 12.72 vs. 37.06 ± 11.84, p = 0.010). Angioedema, emergency referrals, need for systemic steroids, comorbid systemic disorders were more frequent and baseline urticaria control test scores were lower in CSU plus CIndU patients (vs. CIndU, p < 0.001, p = 0.008, p < 0.001, p = 0.031, p = 0.036, respectively). Among CIndU subtypes, ChoU patients were younger (24.9 ± 12.2 vs. 34.47 ± 12.12 vs. 31.38 ± 14.95; p < 0.001) and had male predominance (p < 0.001) while SD patients had no angioedema (p < 0.001) and had higher frequency of increased total IgE levels (p = 0.006)., Conclusions: Isolated CIndU and CSU plus CIndU seems to be different endotypes of CU where CSU plus CIndU presents a more severe and refractory course. There are distinctive features of each CIndU subtype. These suggest involvement of different pathomechanistic pathways in these subtypes that need to be clarified in future studies., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Several adverse cutaneous reactions have been reported in the literature after SARS-CoV-2 vaccination with emerging reports on chronic spontaneous urticaria (CSU). However, there is little literature of chronic urticaria after COVID-19 boosters in a military population and the impact on operational readiness. We present a retrospective case series of CSU following Moderna COVID-19 booster vaccinations at the US Naval Academy (USNA). Demographics, clinical features, and impact on readiness were evaluated. Forty-nine students from the USNA were evaluated for urticaria after their third COVID-19 booster vaccination. Seventeen individuals were diagnosed with CSU. The median age was 20 years and predominantly male; the median time interval between vaccination and the onset of urticaria was 11 days. Out of 13 referred to Allergy, 7 patients had CU index performed and 2 were positive. Four patients received a second booster vaccination subsequently and did not have any exacerbation of symptoms. Symptoms were controlled with antihistamines, and none required immunomodulator or immunosuppressive therapies. All students were able to complete their commissioning, and none were referred for a medical board. In this series, USNA students who developed CSU after the mRNA COVID-19 Moderna booster vaccine did not have limitations from commissioning, duty status, or issues with subsequent COVID-19 vaccinations., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Chronic urticaria (CU) is one of the most common dermatological diseases and has a significant impact on the quality of life of patients. However, the pathogenesis of this disease remains unclear. Autoimmunity in chronic spontaneous urticaria (CSU) has received considerable attention and has been studied previously. Atopy is an important characteristic of CU; however, it has not been fully recognized. Atopy predisposes individuals to immune responses to allergens, leading to type 2 inflammation and immunoglobulin E (IgE) overproduction. Compared with healthy individuals, patients with CU have a higher proportion of atopy, and an atopic background is correlated with the clinical characteristics of CU. The total IgE levels in patients with CU is significantly higher than those in healthy individuals. Although its level is not higher than that in classic allergic diseases, it is closely related to CU. Exogenous allergens, auto-allergens, and specific IgEs, which are closely related to atopy, have been reported, and their roles in CU pathogenesis are also being studied. Local and systemic atopic inflammation is present in patients with CU. This review summarizes the current knowledge regarding atopy and CU, speculating that there are CU subtypes, such as atopic CSU or atopic chronic inducible urticaria (CIndU) and that atopy may be involved in the pathogenesis of CU. These findings provide a new perspective for a comprehensive understanding of the clinical features of CU and further research regarding its pathogenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Yang, Ni and Song.)

There is growing evidence suggesting that in a subset of patients with severe chronic urticaria [CSU] mast cells are activated via mechanisms that bypass the high affinity IgE receptor. This might explain why some patients do not respond at all to anti-IgE therapy [omalizumab]. The present article reviews the pathogenic mechanisms able to lead to histamine release from mast cells described so far in patients with CSU. These include the activation of the coagulation cascade, the activation of the complement system, the activation of the MRGPRX2 receptor, and the platelet activating factor vicious circle. The article suggests some possible interpretations for the clinical events occurring in this specific subset of patients., Competing Interests: Declaration of Competing Interest No conflict of interest to declare, (Copyright © 2023 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Conflicts of interest the authors declare no conflicts of interest.

Background: Chronic spontaneous urticaria (CSU) is an inflammatory skin disease with a complex physiopathology. Serum amyloid A (SAA), an acute-phase reactant, has been proposed as a potential biomarker in urticaria but has yet to be studied in a population with CSU or correlated with disease activity as indicated by the Urticaria Activity Score summed over 7 days (UAS7)., Objective: We sought to determine SAA-1 levels in patients with CSU and correlate them with its activity and control, as well as with clinical features of CSU and other potential blood biomarkers., Methods: We conducted a retrospective multicenter study of 67 patients with CSU, from whom we obtained demographic and clinical data, UAS7 as an indicator of CSU activity, and blood and serum markers., Results: SAA-1 levels positively correlated with UAS7 (r s  = 0.47, P < .001). SAA-1 levels were higher in patients with noncontrolled (UAS7 > 6) CSU than in those with controlled (UAS ≤ 6) CSU (P < .001) and were also higher in patients with concomitant angioedema (P = .003) or delayed pressure urticaria (P = .003)., Conclusion: We propose SAA-1 as a potential biomarker for activity in CSU. Further studies are required to evaluate its potential role as a biomarker for other CSU outcomes, such as response to treatment., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Non-sedating H 1 -antihistamines (nsAH) are the most commonly used treatment for chronic spontaneous urticaria (CSU). Many patients use them as on-demand (OD) therapy rather than a maintenance treatment. Here, we compared OD versus daily maintenance treatment with the nsAH rupatadine, assessed the efficacy of rupatadine updosing, and investigated potential long-term disease-modifying effects., Methods: This multicenter, randomized study consisted of 2 weeks of screening, 8 weeks of double-blind treatment, and 6 weeks of treatment-free follow-up (OD allowed). Adult patients were randomized to 10 mg rupatadine OD or 10 mg rupatadine daily. At Week 4, if patients did not have a complete response, they switched from 10 to 20 mg rupatadine daily or underwent sham updosing (patients on 10 mg rupatadine OD). The primary aim was to compare CSU disease activity at the end of follow-up between daily versus OD. Additionally, we assessed the efficacy of rupatadine updosing. Major outcomes were disease activity, CSU-related quality of life (QoL), and disease control., Results: At Week 4, disease activity and QoL significantly improved in daily versus OD-treated patients. Updosing of rupatadine did not improve the mean disease activity, but the number of complete responders increased during updosing from 5% to 22%. At the end of follow-up, the disease activity of patients treated OD versus daily was not significantly different., Conclusions: Daily rupatadine treatment significantly improved CSU disease activity and QoL during treatment versus OD treatment but not after discontinuation of rupatadine, indicating the benefits of a daily maintenance nsAH schedule., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Chronic urticaria (CU) is the recurring development of wheals (aka "hives" or "welts"), angioedema, or both for more than 6 weeks. Wheals and angioedema occur with no definite triggers in chronic spontaneous urticaria, and in response to known and definite physical triggers in chronic inducible urticaria. Approximately 1.4% of individuals globally will have CU during their lifetime. The itching and physical discomfort associated with CU have a profound impact on daily activities, sexual function, work or school performance, and sleep, causing significant impairment in a patient's physical and mental quality of life. CU also places a financial burden on patients and healthcare systems. Patients should feel empowered to self-advocate to receive the best care. The voice of the patient in navigating the journey of CU diagnosis and management may improve patient-provider communication, thereby improving diagnosis and outcomes. A collaboration of patients, providers, advocacy organizations, and pharmaceutical representatives have created a patient charter to define the realistic and achievable principles of care that patients with CU should expect to receive. Principle (1): I deserve an accurate and timely diagnosis of my CU; Principle (2): I deserve access to specialty care for my CU; Principle (3): I deserve access to innovative treatments that reduce the burden of CU on my daily life; Principle (4): I deserve to be free of unnecessary treatment-related side-effects during the management of my CU; and Principle (5): I expect a holistic treatment approach to address all the components of my life impacted by CU. The stated principles may serve as a guide for healthcare providers who care for patients with CU and translate into better patient-physician communication. In addition, we urge policymakers and authors of CU treatment guidelines to consider these principles in their decision-making to ensure the goals of the patient are achievable., (© 2023. The Author(s).)

Background: Anti-heat shock protein (HSP) autoantibodies are detected in autoimmune diseases. We sought to ascertain whether anti-HSP10 IgG is present in patients with CSU and to elucidate the role of HSP10 in CSU pathogenesis., Method: Using a human proteome microarray, six potential autoantibodies had higher expression in 10 CSU samples compared with 10 normal controls (NCs). Among them, HSP10 IgG autoantibody was quantified by immune dot-blot assay in sera from 86 CSU patients and 44 NCs. The serum levels of HSP10 and microRNA-101-5p were measured in CSU patients and NCs. The effects of HSP10 and miR-101-5p on mast cell degranulation in response to IgE, compound 48/80, and platelet-activating factor (PAF) were investigated., Results: CSU patients had higher IgG positivity to HSP10 (40.7% vs. 11.4%, p = .001), lower serum HSP10 levels (5.8 ± 3.6 vs. 12.2 ± 6.6 pg/mL, p < .001) than in NCs, and their urticaria severity was associated with anti-HSP10 IgG positivity, while HSP10 levels were related to urticaria control status. MiR-101-5p was increased in CSU patients. PAF enhanced IL4 production in PBMCs from CSU patients. IL-4 upregulated miR-101-5p and reduced HSP10 expression in keratinocytes. Transfection of miR-101-5p reduced HSP10 expression in keratinocytes. MiR-101-5p promoted PAF-induced mast cell degranulation, while HSP10 specifically prevented it., Conclusion: A new autoantibody, anti-HSP10 IgG was detected in CSU patients, which showed a significant correlation with UAS7 scores. A decreased serum HSP10 level was associated with upregulation of miR-101-5p due to increased IL-4 and PAF in CSU patients. Modulation of miR-101-5p and HSP10 may be a novel therapeutic approach for CSU., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Purposeof Review: Chronic spontaneous urticaria and chronic inducible urticaria (CSU/CindU) are caused by mast cell and basophil activation leading to degranulation and the release of histamine and several other mediators. Three kinds of factors can trigger mast cells in CSU: (1) activation of stimulating receptor(s) on the mast cell membrane, (2) upregulation of certain receptor(s), and (3) intracellular dysregulation in signaling with overexpression of the spleen tyrosine kinase (SYK) or reduced activation of the inhibitory Src homology 2 (SH2)-containing inositol phosphatases (SHIP)-related pathways. In CSU, two major endotypes exist based on the primary receptor activating mechanism: type I hypersensitivity (IgE-mediated, directed against auto-allergens) and type IIb (autoimmune, via IgG autoantibodies directed against IgE or the IgE-receptor). Their treatment responses vary. We discuss in vitro and in vivo biomarkers., Recent Findings: Patients with auto-allergic CSU have clinical characteristics that can distinguish them partly from those with autoimmune CSU. Most importantly, their disease generally presents a less aggressive course, a better response to second generation (up-dosed) antihistamines and a good response to omalizumab, if necessary. Meanwhile, autoimmune CSU/CindU patients fare less well and often need immunosuppressive drugs. Biomarkers that might help endotype CSU/CindU patients and select the most appropriate treatment, dose, and duration, e.g., for autoallergic CSU, high total IgE and IgE against auto-allergens; for autoimmune CSU, low IgE, basopenia, and IgG against autoantigens like thyroid peroxidase and a positive autologous serum skin test (but sometimes also positive in autoallergy). Some biomarkers are easily accessible but of low specificity; others are highly specific but more futuristic., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Omalizumab (OMA) dramatically improves disease control and quality of life in patients with chronic urticaria (CU)., Objective: We aimed to evaluate the discontinuation patterns of OMA and their determinants in a cohort of French patients with CU., Methods: We conducted a retrospective multicenter study in 9 French tertiary referral hospitals. All patients diagnosed with either spontaneous (CSU) and/or inducible (CIndU) CU who received at least 1 injection of OMA between 2009 and 2021 were included. We analyzed OMA drug survival and investigated possible determinants using Kaplan-Meier curves and log-rank tests., Results: A total of 878 patients were included in this study; 48.8% had CSU, 10.1% CIndU, and 41.1% a combination of both. OMA was discontinued in 408 patients, but the drug was later reintroduced in 50% of them. The main reason for discontinuing treatment was the achievement of a well-controlled disease in 50% of patients. Half of the patients were still being treated with OMA 2.4 years after the initiation of treatment. Drug survival was shorter in patients with CIndU and in those with an autoimmune background. In atopic patients, OMA was discontinued earlier in patients achieving a well-controlled disease. A longer OMA drug survival was observed in patients with a longer disease duration at initiation., Conclusion: In French patients with CU, the drug survival of OMA appears to be longer than that observed in previous studies conducted elsewhere, highlighting discrepancies in prescription and reimbursement possibilities. Further studies are warranted to develop customized OMA treatment schemes based on individual patterns., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Autoimmunity contributes to the pathogenesis of chronic spontaneous urticaria (CSU). The subtyping of CSU has revealed an autoimmune form of CSU. Despite autoimmune diseases having been associated with CSU, there are few prospective studies that have evaluated the characteristics and biomarkers of patients with CSU and autoimmune disease in a real-life practice setting., Objective: To evaluate the presence of specific biomarkers for the presence of autoimmune disease in CSU and to analyze the clinical and therapeutic features of patients with CSU and autoimmune disease., Methods: The clinical, laboratory, and therapeutic features of patients with CSU at a tertiary-level center were prospectively collected. Data obtained were compared in function of the presence/absence of autoimmune disease and typified according to IgE levels., Results: Patients with CSU who had associated autoimmune disease corresponded to middle-aged women with a common pattern of blood test findings: both low baseline IgE and high-affinity receptor of IgE expression, basopenia, eosinopenia, higher baseline erythrocyte sedimentation rate and D-dimer, increased presence of antinuclear antibodies, IgG against thyroid peroxidase, and positive autologous serum skin test result. Total baseline IgE less than or equal to 43.8 IU/mL was both the optimal cutoff to predict autoimmune disease in the CSU cohort and a significant risk factor for the presence of autoimmune disease in the regression analysis., Conclusions: In real-life clinical practice, characteristics of patients with CSU and autoimmune disease share common features with type IIb autoimmune CSU. Total baseline IgE less than or equal to 43.8 IU/mL has been detected as a possible biomarker of autoimmune disease in patients with CSU., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest The authors have no conflicts of interest to disclose.

Background: Although sleep disturbance is known to be common in patients with chronic spontaneous urticaria (CSU), sleep hormone levels in the blood have never before been studied in CSU. Objective: In this study, we aimed to evaluate the serum melatonin levels in patients with CSU. Methods: For the patient group, 80 patients with recently diagnosed CSU, and, for the control group, 75 healthy controls (HC) were included. The study participants' melatonin levels were measured by using the enzyme-linked immunosorbent assay method. CSU disease activity was evaluated by using the urticaria activity score-7 (UAS-7), and the quality of life was assessed with the chronic urticaria quality of life questionnaire (CU-Q2oL). The patients with concomitant diseases likely to affect the melatonin levels or those using related medications were excluded from the study. Results: The patient group consisted of 53 female subjects (67%); the median (interquartile range) age was 34 years (27-43 years). The levels of melatonin were lower in the patients with CSU when compared with the HCs (p < 0.03). The melatonin levels had no significant relationship between UAS-7 and the total scores in CU-Q2oL (p > 0.05). However, a significant negative correlation in the melatonin levels was observed with questions 7 (overall sleep assessment) and 11 (difficulty in falling into sleep) in the CU-Q2oL (r = -0.55 [p < 0.001] and r = -0.62 [p < 0.001], respectively). Conclusion: The presence of low melatonin levels in the patients with CSU suggests that melatonin has a key regulatory role in the CSU development in addition to the deterioration in sleep quality. A new treatment strategy to increase the melatonin levels in CSU may be pursued in further studies to confirm our findings.

Introduction: Chronic spontaneous urticaria (CSU) is mainly manifested as wheals and erythema on the skin accompanied by itching, which will cause emotional anxiety and seriously affect the quality of life in patients. Palmatine (PAL) is a main chemical component of Yajieshaba, which has been found to effectively alleviate the symptoms of food allergy. However, its role and mechanism in CSU remain unclear. The present study aimed to investigate the protective effect of PAL on CSU rats., Methods: We replicated the CSU rat model by intraperitoneal injection of ovalbumin (OVA) in rats on days 0, 2, 4, and 14, with a double dose given on the last challenge. PAL, loratadine and saline were given by gavage from day 5 to day 14. We observed the skin pathologic changes, mast cell degranulation, immune factor levels, inflammatory response and autophagy-related protein expression in CSU rats., Results: We found PAL treatment to be effective in alleviating CSU-like skin lesions and reducing itching and mast cell degranulation in rats. Compared with the OVA group, the levels of immune and inflammatory factors were significantly reduced, neutrophil recruitment was alleviated, suggesting a reduced inflammatory response. The autophagy results showed that PAL further increased the expression of LC3, Beclin-1 and p-LKB1, p-AMPK, Atg5, Atg12 and Atg5-Atg12, while P62 and p-p70S6K1 expression decreased. They collectively suggested that autophagic flux was activated after PAL treatment. However, there was an increase in the expression of LC3I, probably due to the fact that PAL induced its accumulation in order to provide substrate for the generation of more LC3II., Discussion: Overall, PAL had a protective effect on CSU in normal rats, activated the expression of autophagy and improved the inflammatory response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xiao, Yu, Yang and Duan.)

Background: Concern about disease exacerbations and fear of reactions after coronavirus disease 2019 (COVID-19) vaccinations are common in chronic urticaria (CU) patients and may lead to vaccine hesitancy., Objective: We assessed the frequency and risk factors of CU exacerbation and adverse reactions in CU patients after COVID-19 vaccination., Methods: COVAC-CU is an international multicenter study of Urticaria Centers of Reference and Excellence (UCAREs) that retrospectively evaluated the effects of COVID-19 vaccination in CU patients aged ≥18 years and vaccinated with ≥1 dose of any COVID-19 vaccine. We evaluated CU exacerbations and severe allergic reactions as well as other adverse events associated with COVID-19 vaccinations and their association with various CU parameters., Results: Across 2769 COVID-19-vaccinated CU patients, most (90%) received at least 2 COVID-19 vaccine doses, and most patients received CU treatment and had well-controlled disease. The rate of COVID-19 vaccination-induced CU exacerbation was 9%. Of 223 patients with CU exacerbation after the first dose, 53.4% experienced recurrence of CU exacerbation after the second dose. CU exacerbation most often started <48 hours after vaccination (59.2%), lasted for a few weeks or less (70%), and was treated mainly with antihistamines (70.3%). Factors that increased the risk for COVID-19 vaccination-induced CU exacerbation included female sex, disease duration shorter than 24 months, having chronic spontaneous versus inducible urticaria, receipt of adenovirus viral vector vaccine, having nonsteroidal anti-inflammatory drug/aspirin intolerance, and having concerns about getting vaccinated; receiving omalizumab treatment and Latino/Hispanic ethnicity lowered the risk. First-dose vaccine-related adverse effects, most commonly local reactions, fever, fatigue, and muscle pain, were reported by 43.5% of CU patients. Seven patients reported severe allergic reactions., Conclusions: COVID-19 vaccination leads to disease exacerbation in only a small number of CU patients and is generally well tolerated., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Summary: The hunt for the causes and pathogenic mechanisms involved in chronic spontaneous urticaria (CSU) has engaged clinicians and scientists for decades. Although not all aspects of the disease are defined, our knowledge has now improved to the point that we can consider CSU as an umbrella clinical phenotype under which several different endotypes probably exist. The present article will briefly summarize the fascinating history of the progress in our knowledge of this disease.

Background: The Urticaria Control Test (UCT) is a well-established, very easy to use and calculate 4-item patient-reported outcome measure to assess chronic urticaria disease control during the previous 4 weeks. Clinical trials and practice may benefit from the use of a UCT version with a shorter recall period, but this does not exist., Objectives: We sought to develop and validate a UCT version with a 7-day recall period, the UCT7., Methods: The UCT7 was developed, based on the UCT, and tested, in 152 patients with chronic urticaria (spontaneous: n = 101, inducible: n = 51) for its reliability, validity and screening accuracy, and clinimetric properties, in other words, the cutoff for well-controlled disease and the minimal clinically important difference., Results: The UCT7 showed excellent internal consistency reliability with a Cronbach αvalue of 0.91 and test-retest reliability with an intraclass correlation coefficient of 0.83. Convergent validity was high and strongly correlated with anchors of disease control, wheal and angioedema frequency, and urticaria-related quality of life impairment. The UCT7 showed excellent sensitivity to change; however, changes in angioedema activity and impact did not correlate well with changes in UCT7. Based on receiver-operating characteristic curve analysis, the proportion of correctly classified patients, and patients' assessment of treatment efficacy, we recommend a cutoff value of 12 points for identifying patients with well-controlled disease. The UCT7 minimal clinically important difference for improvement was estimated to be 2 points., Conclusions: The UCT7 is a validated 7-day recall period version of the UCT. It is ideal for the assessment of disease control at short intervals in patients with chronic urticaria in clinical studies and practice., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Studies of cold-induced urticaria (ColdU) in pediatric patients are limited and not well characterized. Objective: The objective of the study was to investigate the characteristics of ColdU in children. Methods: A multicenter, retrospective chart review was performed in children ages ≤18 years diagnosed with ColdU at 11 pediatric allergy and immunology centers in Turkey between September 1, 2010, and August 31, 2022. Results: A total of 83 children with ColdU were included, 54.2% were girls, and the mean age of symptom onset was 8.8 years. The median duration of ColdU at the time of diagnosis was significantly higher in the girls than in the boys (1.0 years [0.0-13.8 years] versus 0.3 years [0.0-15.0 years]; p = 0.007). All the patients underwent an ice cube test, and 71.1% were found positive (typical ColdU). The mean ± standard deviation age of onset was significantly higher in the patients with typical ColdU versus atypical patients (9.4 ± 4.5 years versus 7.3 ± 4.5 years; p = 0.041). Swimming alone and in combination with the wind were significantly the most reported triggers in patients with cold-induced anaphylaxis (ColdA) when compared with patients with ColdU and with nonanaphylactic symptoms (70.0% versus 28.9% [p = 0.022], and 50.0% versus 4.1% [p < 0.001], respectively). Only patients with other chronic urticaria were found to be associated with the development of typical ColdU (p = 0.036). The median total serum immunoglobulin E (IgE) was significantly higher in typical ColdU than in atypical patients (72.5 IU/mL [3.86 - 2500 IU/mL] versus 30.0 IU/mL [0.83 - 1215 IU/mL]; p = 0.007); however, total serum IgE differences were not found to affect ColdU resolution between the two groups (p = 0.204). The resolution was documented in 30.4%. Conclusion: Those who were boys and had a positive ice cube test result could have an association with earlier onset of ColdU. Those swimming alone on a windy day were at highest risk for ColdA. It is still unclear what characteristics are associated with the resolution of ColdU, and this warrants further investigation.

Chronic urticaria is very common in clinic, but its pathogenesis is not fully elucidated. Most patients can't find the exact cause, resulting in misdiagnosis or delayed treatment. Previous studies have found that mast cell activation is the central link in the pathogenesis of chronic urticaria. Genetics, autoimmune, coagulation disorders, and infection may also be involved in the pathophysiological process of chronic urticaria. With the deepening of research, more immune and non-immune mechanisms have been gradually revealed in the pathogenesis of chronic urticaria, such as the interaction of immune cells in the microenvironment of urticaria, intestinal flora and metabolism, neuroimmunity, environmental factors and hormones. Clarifying the pathogenesis of chronic urticaria will help to find more treatment targets and provide more diversified ideas for clinical diagnosis and treatment.

Purpose of Review: The purpose of this review is to provide an overview of the recent advancements and relevance of the autoimmune theories in chronic spontaneous urticaria (CSU)., Recent Findings: Two primary types of autoimmunity, Type I and Type IIb, have emerged as major contributors to CSU, characterized by immunoglobulin E (IgE) and immunoglobulin G (IgG) autoantibodies, respectively. Genetic evidence supports the notion that CSU shares more similarities with other autoimmune diseases rather than atopic diseases. Novel autoallergens such as FcεRI and tissue transglutaminase have been identified, contributed to our understanding of autoimmune mechanisms. Furthermore, the potential overlap between Type I and Type IIb autoimmunity has been recognized. Evaluating the autoimmune status of CSU patients through biomarkers and understanding their clinical implications is vital for effective management. For instance, CSU patients with Type IIb autoimmunity, with or without coexisting Type I autoimmunity, may exhibit resistance to H1-antihistamines and omalizumab treatment but could potentially respond well to cyclosporine or Bruton's tyrosine kinase inhibitors., Summary: Further investigations are needed to explore new autoallergens and autoantibodies in CSU, establishing their connection to the development of autoimmunity. The efficacy of novel drugs targeting different mechanisms should be examined to determine their responses in both autoimmune CSU and nonautoimmunity-related CSU., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Chronic urticaria (CU) is a systemic disorder which is characterized by recurrent wheals and/or angioedema lasting more than 6 weeks. Sex hormones have been suggested to play a role in CU pathogenesis, however, their clinical implications have not been adequately described in the literature., Objective: To determine whether conditions that change sex hormone levels such as puberty, menstruation, pregnancy, breastfeeding, and menopause affect the course of CU., Methods: This cross-sectional questionnaire study was conducted on female CU patients at Okmeydani Training and Research Hospital UCARE Center between 2016 and 2017. The open-ended questionnaire consisted of questions evaluating the effects of hormonal changes on disease course., Results: A total of 111 female CU patients were included in the analysis. During the perimenstrual period, CU symptoms worsened in 29% of patients but improved in 4.8%. The disease course did not change in the majority of patients during puberty, pregnancy, lactation, or menopause (100%, 96%, 83.8%, and 95.6%, respectively)., Conclusions: Contrary to expectations, a change in sex hormone levels had no effect on the course of CU in the majority of cases. However, disease activity increased in one-third of CU patients during the perimenstrual period., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Chronic urticaria is a common condition presenting with intensely pruritic wheals. Although individual lesions resolve within 24 hours, by definition, chronic urticaria lasts for a duration of at least 6 weeks. Both spontaneous and inducible forms exist. In the spontaneous variant, chronic urticaria occurs in the absence of clearly identifiable triggers. In chronic inducible urticaria, specific triggers may include dermatographism, cholinergic (heat), cold, exercise, delayed pressure, and solar. Extensive laboratory evaluation for chronic spontaneous urticaria is not required unless indicated by clinical history or physical examination. Angioedema describes sudden onset of localized edema involving the deep layers of the skin and submucosal tissues. It can be seen in isolation or in conjunction with chronic urticaria. Angioedema typically resolves slower than wheals, taking up to 72 hours or longer. Histamine- and bradykinin-mediated forms exist. Both chronic urticaria and angioedema have many mimics, and a broad range of differential diagnoses should be considered. Importantly, an incorrect diagnosis may have significant implications for the additional investigation, treatment, and prognosis of the affected patient. The aim of this article is to discuss the characteristics of chronic urticaria and angioedema, and an approach to the investigation and diagnosis of their mimics., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Chronic spontaneous urticaria (CSU) is a dermatological disorder accompanied by itching that greatly affects the quality of life and quality of sleep. Therefore, it is assumed that CSU patients consequently experience reduced melatonin secretion and lower values of serum or salivary melatonin. This pilot study included 20 patients with CSU (chronic urticaria of unknown etiology that lasts for more than 6 weeks) and 10 healthy controls. All subjects were examined by a dermatovenereologist-allergist, as well as an oral pathologist, to exclude oral pathological conditions. Salivary melatonin levels were determined by ELISA and all subjects completed a standardized Dermatology Life Quality Index questionnaire and Pittsburgh Sleep Quality Index on the same day they gave a saliva sample for analysis. According to our results, 86% of CSU patients had decreased values of salivary melatonin, and lower salivary melatonin values significantly correlated with a reduced quality of life in CSU patients. This study was the first to analyze melatonin in CSU patients, also suggesting a possible new therapeutic option for the treatment of CSU., (Sestre Milosrdnice University Hospital.)

Background: Two endotypes of chronic spontaneous urticaria (CSU) associated with mast cell-activating autoantibodies are described, namely autoallergic chronic spontaneous urticaria (aaCSU; with immunoglobulin E [IgE]-anti-autoallergens) and autoimmune chronic spontaneous urticaria (aiCSU; with IgG-anti-high-affinity receptor for the Fc region of immunoglobulin E [FcεRI]/IgE)., Objective: To investigate the rates of CSU patients with aaCSU and aiCSU., Methods: We analyzed 111 CSU patients for aaCSU (ie, IgE to thyroid peroxidase, interleukin 24) and for aiCSU (ie, a positive autologous serum skin and Basophil Activation Test plus immunoglobulin G [IgG]-anti-FcεRI/IgE). Clinical and laboratory parameters were compared in patients with aaCSU, aiCSU, and both., Results: Across 111 patients with CSU, 64 (58%) had aaCSU and 9 (8%) had aiCSU. Eight of the 9 aiCSU patients had aaCSU, but only 8 of 64 patients with aaCSU had aiCSU. In total, 7% (8 of 111) of patients had both aiCSU and aaCSU, 41% (46 of 111) had neither, and 16% (18 of 111) tested negative for all markers of aaCSU and aiCSU assessed. Patients with aaCSU or aiCSU are different from those without: patients with stand-alone aaCSU tend to be younger than non-aaCSU patients, aiCSU, and aaCSU/aiCSU overlapping subpopulations. In contrast, patients with aiCSU, with or without aaCSU coexistence, are more often female, have higher levels of thyroid peroxidase autoantibodies (both IgG and IgE), and show more severe quality of life impairment., Conclusions: Our novel finding that aiCSU coexisting with aaCSU needs to be confirmed in bigger cohorts and multicenter studies. Autoimmunity driven by autoreactive IgE and/or IgG in CSU needs further investigation for better understanding of the pathophysiology., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Chronic spontaneous urticaria (CSU) is a frequent and often severely disabling disease. A large number of studies were performed during the last 2 decades to clarify its pathogenesis. These studies shed light on the underlying autoimmune mechanisms of CSU pathogenesis and have led us to understand that different mechanisms may exist and, sometimes, coexist behind the same clinical presentation. The present article reviews the meaning of the terms autoreactivity, autoimmunity, and autoallergy, which have been variably used over the years to define different endotypes of the disease. Furthermore, we discuss the methods potentially able to lead us to the correct classification of CSU patients., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Chronic urticaria is a disease that can significantly impact a patient's quality of life and ability to function. There are effective treatment options, such as nonsedating antihistamines or biologics, but some patients do not respond to these therapies, or the therapies are not available or affordable to all patients. This review aims to summarize potential treatment strategies for patients (1) who do not respond to antihistamines and (2) cannot readily access or do not respond to biologics. The review emphasizes the importance of sound clinical practice, including correct diagnosis of chronic urticaria phenotypes, treatment of associated comorbidities, and consideration of add-on pharmacological and nonpharmacological approaches. Although some treatments may lack high-quality evidence, they may still be justifiable in certain cases, provided that there is shared decision-making, regular reassessment, and early recognition of adverse events., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Chronic urticaria (CU) is a common chronic inflammatory disease, but the burden on quality of life (QOL) has been underestimated., Objective: To compare QOL among patients with CU and those with other chronic diseases., Methods: Adult patients who visited a referral hospital for CU were enrolled. Patients completed self-reported questionnaires including clinical characteristics of chronic urticaria and the short form 36 health survey. As a comparative group, patients with rheumatoid arthritis, patients with diabetes treated with insulin, patients on maintenance hemodialysis, and healthy controls were enrolled and completed the short form 36 health survey., Results: In all, 119 patients with CU were enrolled and their short form 36 scores were not significantly different from those of healthy controls. However, patients with CU with poor responses to treatment showed impaired QOL to a degree similar to that of patients with rheumatoid arthritis or insulin-treated diabetes. The patients with CU showed various clinical characteristics with respect to treatment response, accompanying symptoms, and aggravating factors. Among these factors, pain at the urticarial lesion and symptom aggravation during exercise and after the consumption of certain foods were related with lower QOL., Conclusions: Patients with CU with an incomplete response to treatment had significantly low QOL, comparable to that of patients with rheumatoid arthritis or insulin-treated diabetes. To minimize this effect, clinicians should aim to control symptoms and aggravating factors., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Panic disorder and panic attacks are two of the most common problems in psychiatry. A psychoimmunological correlation between allergic diseases and panic disorder has been strongly suggested. Histamine H1 receptor antagonists have been suggested as alternative drugs for the treatment of panic disorder. Chronic spontaneous urticaria (CSU) and panic disorder improved simultaneously with selective serotonin reuptake inhibitor antidepressants. Panic disorder has also been treated with the antihistamine chlorpheniramine. The immunoglobulin/histamine complex is a histamine-fixed immunoglobulin preparation that was reported to be effective in treating CSU. This case report describes the successful treatment of a patient with concomitant panic disorder and CSU for 23 years using immunoglobulin/histamine complex therapy., Case Presentation: This report describes a 52-year-old female Korean patient who suffered from CSU with panic disorder for 23 years. Basic allergy tests (blood tests and skin prick tests) were conducted before and after treatment for the evaluation of allergic conditions. A multiple allergosorbent test (MAST) for the detection of allergen-specific IgE levels was also performed. The clinical severity of CSU was evaluated using the urticaria severity score system. Diagnostic interviews systematically assessed the diagnostic criteria outlined by the DSM-V, and the patient was evaluated before, during and after treatment using the Beck Depression Inventory (BDI-2) for depression, the State-Trait Anxiety Inventory (STAI) for anxiety and the Beck Hopelessness Score (BHS) for hopelessness. The patient received 2 ml of Histobulin™ (12 mg human immunoglobulin/0.15 µg histamine complex) once a week by subcutaneous injection for the treatment of CSU. Initial improvement of CSU was achieved after the third injection. After the twenty-seventh injection of Histobulin™, she showed no symptoms or signs and ceased allergic medication use. With the remission of CSU, allergic rhinitis was also completely resolved. The frequency of the common cold was significantly decreased during and after treatment. The medication frequency and development of clinical manifestations of panic disorder changed in parallel with the clinical severity of CSU. Moreover, the patient exhibited no clinical manifestations and ceased medication for panic disorder and sleeping pills for insomnia simultaneously with the remission of CSU. In the psychological evaluation, the BDI, STAI and BHS scores improved accordingly., Conclusions: The immunoglobulin/histamine complex was effective in treating CSU and concomitant panic disorder in this patient and could be effective in treating some types of panic disorder. Considering the mechanisms of action of histamine and the immunoglobulin/histamine complex together with the patient's clinical progress, histamine seemed to be related to panic disorder in this case. The concept of histamine-mediated syndromes, including allergies and psychiatric disorders, shows that a wider disease identity may be needed. Further studies on the immunopathogenesis of panic disorder and the mechanisms of action of the immunoglobulin/histamine complex are necessary., (© 2023. The Author(s).)